90Y-Ibritumomab Tiuxetan (Zevalin®) Consolidation of First Remission in Advanced Stage Follicular Non-Hodgkin’s Lymphoma: First Results of the International Randomized Phase 3 First-Line Indolent Trial (FIT) in 414 Patients.
Bibliographic record
Abstract
Abstract Radioimmunotherapy is effective in patients with relapsed/refractory and newly diagnosed follicular non-Hodgkin’s lymphoma (FL). This study investigated the efficacy and safety of Zevalin consolidation in patients with advanced stage FL responding to first-line chemotherapy. The concept tested was whether a single infusion of Zevalin would prolong progression free survival (PFS) in patients with (minimal) residual disease. Major inclusion criteria were: CD20-positive grade 1 or 2 FL; stage III or IV at diagnosis; normal peripheral blood cell counts; <25% bone marrow involvement; age ≥18 yrs, and CR/CRu or PR after first line chemotherapy determined by physical examination, CT scans and bone marrow biopsy. From 8/2001 to1/2005, 414 patients were enrolled at 77 study centers in 12 European countries and Canada. After completing induction therapy, patients were randomized to receive either Zevalin (250 mg/m2 rituximab on day -7 and on day 0 followed on day 0 by Zevalin 0.4 mCi/kg; maximal dose: 32 mCi;[n=208]) or no further treatment [n=206]). The primary end point was prolongation of PFS, calculated from randomization, which was approximately 2 wks before Zevalin administration. Secondary end points were change of response status, ie, PR to CR/CRu and BCL2-JH PCR status from positive to negative; safety/tolerability and quality of life. Patient demographics were similar in both groups (Zevalin/control): males 48%/50%; median age 55/53 yrs; at diagnosis, stage III 35%/31%, stage IV 64%/66%; B-symptoms 22%/20%; response status after induction, PR 49%/47%; CR: 51%/53%. Induction therapies included: CVP n=106, CHOP (-like) n=188, fludarabine combinations n=22, chlorambucil n=39 and rituximab-chemotherapy combinations n=59. With a median follow-up of 2.9 yrs, the median PFS increased from 13.5 (controls) to 37 mo (Zevalin; p<0.0001; HR 0.463). For patient subgroups in PR or CR after induction, median PFS was 6.3 vs 29.7 mo (p<0.0001; HR 0.304) and 29.9 vs 54.6 mo (p=0.01; HR 0.609), respectively. After Zevalin consolidation, 77% of patients in PR after induction therapy converted to CR; in total, 87% of patients were in CR(u), 76% in CR and 11% in CRu. Subgroup analyses based on induction treatment and outcome according to FLIPI will be presented. Toxicity was primarily hematologic. Median platelet count nadir was 45x109/L; range 8–404x109/L) at wk 7 (∼5 wks post Zevalin); median neutrophil nadir was 1.0x109/L (range 0.02–6.6x109/L) at wk 8(∼ 6 wks post Zevalin). Grade 3/4 infections occurred in 16 (8%) patients after Zevalin vs 5 (2%) in the control arm. So far, 11 patients have died, 5 in control arm (1 sepsis, 4 progressive disease); 6 in Zevalin arm (1 neutropenic sepsis after subsequent chemotherapy, 1 pancreas carcinoma, 1 AML, 3 progressive disease). Conclusion: Zevalin consolidation of first remission in advanced stage FL is highly effective, resulting in a total CR(u) rate of 87% and prolongation of PFS by 2 yrs, with a favorable toxicity profile.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".